Backdoor pathway for dihydrotestosterone biosynthesis: Implications for normal and abnormal human sex development

  title={Backdoor pathway for dihydrotestosterone biosynthesis: Implications for normal and abnormal human sex development},
  author={Maki Fukami and Keiko Homma and Tomonobu Hasegawa and Tsutomu Ogata},
  journal={Developmental Dynamics},
We review the current knowledge about the “backdoor” pathway for the biosynthesis of dihydrotestosterone (DHT). While DHT is produced from cholesterol through the conventional “frontdoor” pathway via testosterone, recent studies have provided compelling evidence for the presence of an alternative “backdoor” pathway to DHT without testosterone intermediacy. This backdoor pathway is known to exist in the tammar wallaby pouch young testis and the immature mouse testis, and has been suggested to be… 
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The backdoor pathway to dihydrotestosterone
  • R. Auchus
  • Biology
    Trends in Endocrinology & Metabolism
  • 2004
Clinical implications of androgen synthesis via 5alpha-reduced precursors.
An alternate pathway to DHT was elucidated in the tammar wallaby pouch young, and studies in knockout mice showed that this pathway uses 5alpha-reductase type 1 to convert 17-hydroxyprogesterone to 5 alpha-reduced androgen precursors.
Increased activation of the alternative "backdoor" pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis.
The elevated ratios of pdiol to the Δ4 and Δ5 pathway metabolites as well as the higher androsterone to etiocholanolone ratio in patients with 21-OHD indicate postnatal activity of the backdoor pathway with maximum activity during early infancy.
Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase deficiency: implication for the backdoor pathway to dihydrotestosterone.
The increased androsterone excretion during early infancy, as compared with the etiocholanolone and 11-hydroxyandrostersone excretions in the same period, suggests the presence of the backdoor pathway in PORD.
Disorders of Androgen Synthesis – from Cholesterol to Dehydroepiandrosterone
  • W. Miller
  • Biology, Medicine
    Medical Principles and Practice
  • 2005
Androgens and estrogens are primarily made from dehydroepiandrosterone (DHEA), which is made from cholesterol via four steps, which is regulated posttranslationally by at least three factors: the abundance of the electron-donating protein P450 oxidoreductase (POR), the presence of cytochrome b5 and the serine phosphorylation of P450c17.
New frontiers in androgen biosynthesis and metabolism
  • T. Penning
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    Current opinion in endocrinology, diabetes, and obesity
  • 2010
Recent advances have identified enzymes that regulate ligand access to the androgen-receptor; a ‘backdoor pathway’ to 5α-DHT that does not require testosterone acting as an intermediate; and the finding that castrate-resistant prostate cancer has undergone an adaptive response to androgen deprivation.
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Genetic and Clinical Features of P450 Oxidoreductase Deficiency
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